tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-2-formylphenylcarbamate | 335672-45-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-2-formylphenylcarbamate
• 英文别名: tert-butyl N-[5-[tert-butyl(dimethyl)silyl]oxy-2-formylphenyl]carbamate
• CAS: 335672-45-2
• 化学式: C₁₈H₂₉NO₄Si
• 分子量: 351.518
• InChiKey: GLGKQCBIJWVRQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.23
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-2-formylphenylcarbamate 在 哌啶 、 盐酸 、 copper(l) iodide 、 18-冠醚-6 、 四丁基氟化铵 、 sodium hydride 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 (1R,9S,12S)-7-Ethyl-4,8-dioxo-12-vinyl-7-aza-tricyclo[7.2.1.0^1,6]dodeca-2,5-diene-9-carboxylic acid methyl ester
  参考文献：
  名称：

  经由通用中间体制备用于合成甲基卡可尼碱和消旋马宁的高级中间体

  摘要：

  1和2的多环前体是通过共同的中间体制备的。关键步骤包括苯酚的分子内烷基化和金属氨选择性还原。

  DOI：

  10.1016/j.tetlet.2004.12.092
• 作为产物：
  描述：

  3-羟基苯基氨基甲酸叔丁酯 在 咪唑 、 叔丁基锂 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 、 正戊烷 为溶剂， 反应 3.0h， 生成 tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-2-formylphenylcarbamate
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells

  摘要：

  Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential therapeutic targets to limit cancer progression. In this study, we have developed and implemented a stepwise in vitro screening procedure on human cancer cells to identify new potent MCT inhibitors. Various 7-substituted carboxycoumarins and quinolinone derivatives were synthesized and pharmacologically evaluated. Most active compounds were obtained using a palladium-catalyzed Buchwald-Hartwig type coupling reaction, which proved to be a quick and efficient method to obtain aminocarboxycoumarin derivatives. Inhibition of lactate flux revealed that the most active compound 19 (IC50 11 nM) was three log orders more active than the CHC reference compound. Comparison with warfarin, a conventional anticoagulant coumarin, further showed that compound 19 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.010

文献信息

• Tyrosine kinase inhibitors
  申请人：Merck & Co., Inc.

  公开号：US06479512B1

  公开（公告）日：2002-11-12

  The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

  本发明涉及抑制、调节和/或调控酪氨酸激酶信号转导的化合物，含有这些化合物的组合物，以及利用它们治疗哺乳动物中依赖于酪氨酸激酶的疾病和病况的方法，如血管生成、癌症、肿瘤生长、动脉粥样硬化、年龄相关性黄斑变性、糖尿病视网膜病变、炎症性疾病等。
• Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells
  作者：Nihed Draoui、Olivier Schicke、Antony Fernandes、Xavier Drozak、Fady Nahra、Amélie Dumont、Jonathan Douxfils、Emmanuel Hermans、Jean-Michel Dogné、Romu Corbau、Arnaud Marchand、Patrick Chaltin、Pierre Sonveaux、Olivier Feron、Olivier Riant

  DOI：10.1016/j.bmc.2013.09.010

  日期：2013.11

  Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential therapeutic targets to limit cancer progression. In this study, we have developed and implemented a stepwise in vitro screening procedure on human cancer cells to identify new potent MCT inhibitors. Various 7-substituted carboxycoumarins and quinolinone derivatives were synthesized and pharmacologically evaluated. Most active compounds were obtained using a palladium-catalyzed Buchwald-Hartwig type coupling reaction, which proved to be a quick and efficient method to obtain aminocarboxycoumarin derivatives. Inhibition of lactate flux revealed that the most active compound 19 (IC50 11 nM) was three log orders more active than the CHC reference compound. Comparison with warfarin, a conventional anticoagulant coumarin, further showed that compound 19 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux. (C) 2013 Elsevier Ltd. All rights reserved.
• Preparation of advanced intermediates for the synthesis of both methyllycaconitine and racemulsonine via a common intermediate
  作者：George A. Kraus、Sarathy Kesavan

  DOI：10.1016/j.tetlet.2004.12.092

  日期：2005.2

  Polycyclic precursors to 1 and 2 have been prepared via a common intermediate. The key steps include the intramolecular alkylation of a phenol and a selective metal–ammonia reduction.

  1和2的多环前体是通过共同的中间体制备的。关键步骤包括苯酚的分子内烷基化和金属氨选择性还原。